tbuckley/cabot-search huggingface dataset:
Incremental Strategies for Providing Health Insurance for the Uninsured
Authors: Kenneth E. Thorpe
Journal: JAMA (1997)

<h3>Objective.</h3> —To present several incremental strategies for extending health insurance coverage for segments of an estimated 40.6 million uninsured persons in the United States. Along with these strategies, the federal costs and estimates of the number of newly insured are presented. <h3>Design.</h3> —Using data from the Congressional Budget Office and the federal government, the number of newly insured persons in the United States under options designed to increase coverage among uninsured children, their parents, and workers between jobs are simulated. The federal costs and coverage implications of these options are estimated for federal fiscal years 1998 through 2002. <h3>Methods.</h3> —Three distinct incremental approaches for covering the uninsured are explored. The first approach would expand coverage through the current Medicaid program. The second approach would provide financial incentives for parents of children eligible for Medicaid to purchase coverage, and the final approach provides time-limited subsidies allowing workers and their families to purchase insurance when they are between jobs. <h3>Main Results.</h3> —The federal costs of these approaches range from $2 billion to $3 billion per year (enrollment outreach approach) to $5 billion to $7 billion per year (enrolling parents of Medicaid-eligible children approach). If pursued simultaneously, the incremental strategies under investigation could extend health insurance to more than 7 million uninsured persons in the United States. The cost of these options could be financed through Medicaid savings, restructuring the current disproportionate share payments made through Medicare and Medicaid, increasing excise taxes on tobacco, or all of the above. <h3>Conclusions.</h3> —The incremental strategies would build on the current US health care delivery system by providing targeted financial assistance to specific populations. By their nature, such reforms could provide a political means for compromise and agreement between Congress and the president. Though the reforms do not, by design, provide a comprehensive solution to the problems facing the uninsured, they would address the severe problems facing many low- and middle-income families unable to purchase health insurance today.
Risk of connective tissue disease among women with breast implants
Authors: D R. Shanklin, D. L Smalley
Journal: BMJ (1998)

How to use the Risk Tables1 To estimate a person's absolute annual risk of a cardiovascular event (newly diagnosed angina, MI, CHD death, stroke or TIA) identify the table relating to person's sex, diabetes status, smoking status and age (locate closest) 2 Within the table find the cell nearest to the person's blood pressure and TC:HDL-C ratio 3 Compare cell colour with risk level 4 For patients with a strong family history of CHD, increase their risk level by at least one colour category
Development and validation of an abnormality-derived deep-learning diagnostic system for major respiratory diseases
Authors: Chengdi Wang, Jiechao Ma, Shu Zhang, Jun Shao, Yanyan Wang, Hong-Yu Zhou, Lujia Song, Jie Zheng, Yizhou Yu, Weimin Li
Journal: npj Digital Medicine (2022)

Respiratory diseases impose a tremendous global health burden on large patient populations. In this study, we aimed to develop DeepMRDTR, a deep learning-based medical image interpretation system for the diagnosis of major respiratory diseases based on the automated identification of a wide range of radiological abnormalities through computed tomography (CT) and chest X-ray (CXR) from real-world, large-scale datasets. DeepMRDTR comprises four networks (two CT-Nets and two CXR-Nets) that exploit contrastive learning to generate pre-training parameters that are fine-tuned on the retrospective dataset collected from a single institution. The performance of DeepMRDTR was evaluated for abnormality identification and disease diagnosis on data from two different institutions: one was an internal testing dataset from the same institution as the training data and the second was collected from an external institution to evaluate the model generalizability and robustness to an unrelated population dataset. In such a difficult multi-class diagnosis task, our system achieved the average area under the receiver operating characteristic curve (AUC) of 0.856 (95% confidence interval (CI):0.843-0.868) and 0.841 (95%CI:0.832-0.887) for abnormality identification, and 0.900 (95%CI:0.872-0.958) and 0.866 (95%CI:0.832-0.887) for major respiratory diseases' diagnosis on CT and CXR datasets, respectively. Furthermore, to achieve a clinically actionable diagnosis, we deployed a preliminary version of DeepMRDTR into the clinical workflow, which was performed on par with senior experts in disease diagnosis, with an AUC of 0.890 and a Cohen's k of 0.746-0.877 at a reasonable timescale; these findings demonstrate the potential to accelerate the medical workflow to facilitate early diagnosis as a triage tool for respiratory diseases which supports improved clinical diagnoses and decision-making.
Determining drug dose in the era of targeted therapies: playing it (un)safe?
Authors: Sigrid S. Skånland, Geir E. Tjønnfjord
Journal: Blood Cancer Journal (2022)

Abstract Targeted therapies against phosphatidylinositol 3-kinase (PI3K), Bruton’s tyrosine kinase (BTK), and B-cell lymphoma-2 (BCL-2) are approved for chronic lymphocytic leukemia (CLL). Since approval of the first-in-class drugs, next-generation agents have become available and are continuously under development. While these therapies act on well-characterized molecular targets, this knowledge is only to some extent taken into consideration when determining their dose in phase I trials. For example, BTK occupancy has been assessed in dose-finding studies of various BTK inhibitors, but the minimum doses that result in full BTK occupancy were not determined. Although targeted agents have a different dose–response relationship than cytotoxic agents, which are more effective near the maximum tolerated dose, the traditional 3 + 3 toxicity-driven trial design remains heavily used in the era of targeted therapies. If pharmacodynamic biomarkers were more stringently used to guide dose selection, the recommended phase II dose would likely be lower as compared to the toxicity-driven selection. Reduced drug doses may lower toxicity, which in some cases is severe for these agents, and are supported by retrospective studies demonstrating non-inferior outcomes for patients with clinically indicated dose reductions. Here, we review strategies that were used for dose selection in phase I studies of currently approved and select investigational targeted therapies in CLL, and discuss how our initial clinical experience with targeted therapies have pointed to dose reductions, intermittent dosing, and drug combinations as strategies to overcome treatment intolerance and resistance.
A pan-Zea genome map for enhancing maize improvement
Authors: Songtao Gui, Wenjie Wei, Chenglin Jiang, Jingyun Luo, Lu Chen, Shenshen Wu, Wenqiang Li, Yuebin Wang, Shuyan Li, Ning Yang, Qing Li, Alisdair R. Fernie, Jianbing Yan
Journal: Genome biology (2022)

Abstract Background Maize ( Zea mays L.) is at the vanguard facing the upcoming breeding challenges. However, both a super pan-genome for the Zea genus and a comprehensive genetic variation map for maize breeding are still lacking. Results Here, we construct an approximately 6.71-Gb pan- Zea genome that contains around 4.57-Gb non-B73 reference sequences from fragmented de novo assemblies of 721 pan- Zea individuals. We annotate a total of 58,944 pan- Zea genes and find around 44.34% of them are dispensable in the pan- Zea population. Moreover, 255,821 common structural variations are identified and genotyped in a maize association mapping panel. Further analyses reveal gene presence/absence variants and their potential roles during domestication of maize. Combining genetic analyses with multi-omics data, we demonstrate how structural variants are associated with complex agronomic traits. Conclusions Our results highlight the underexplored role of the pan- Zea genome and structural variations to further understand domestication of maize and explore their potential utilization in crop improvement.
Letter to the editor: Fatty liver and mortality in populations who are elderly
Authors: Yanrong Sun, Junwei Zhang, Hanfei Wang, Wenjuan Wang, Huiru Ding, Yiyao Xu, Lihua Qin
Journal: Hepatology (2022)

To the editor, The study by van Kleef et al. showed that the presence of fatty liver disease was not associated with mortality in their cohort. The authors finally concluded that screening for fatty liver disease and/or fibrosis was unlikely to improve outcomes among the people who were elderly.1 We are very interested in this innovative opinion, but there are remaining questions. First, the authors adjusted for several factors in the multivariable‐adjusted analysis. However, some of these factors are closely related to fatty liver, such as individual components of the metabolic syndrome, heart failure, coronary heart disease, and stroke. The relationship between fatty liver and these factors needs to be further explained. Second, among participants with cause‐specific mortality data (344/793), only one died of liver‐related death. Such low liver‐related mortality may be because of the short median follow‐up period of 6.2 years, because another study with a median follow‐up of 14.2 years reported 4338 deaths among 10,568 patients with fatty liver.2 The relative importance of liver‐related deaths may be lower and overshadowed by cardiovascular and cancer‐related deaths in people who are elderly in a short period. In addition, few recorded deaths yield imprecise risk estimates and poor generalizability. Third, the research reported that the epidemiology of NAFLD had sexual dimorphism, and the incidence of liver‐related death was higher in men before the age of 70 but higher in women afterward. The incidence of liver‐related death in women increased from 0.62 to 7.14 per 10,000 person‐years from age 60–69 years to 70–79 years.3 42.7% of the 4093 participants in this study were male, further studies of the relationship between elderly fatty liver and mortality by sex may generate innovative hypotheses. Finally, previous studies have shown that fatty liver significantly increases risks of overall mortality and mortality in a dose‐dependent manner with worsening NAFLD severity.4 Substantial evidence linked fatty liver severity with an increased risk of fatal disease events. Liver biopsy is the gold standard for assessing steatosis and fibrosis. The effect of fatty liver on cause‐specific mortality may differ if invasive biopsy parameters are used to diagnose different steatosis grades.
Reply
Authors: Laurens A. van Kleef, Robert J. de Knegt, Willem Pieter Brouwer
Journal: Hepatology (2022)

We appreciate the interest of Jing et al. in our recently published manuscript that demonstrated that MAFLD and excessive alcohol consumption were both simultaneous predictors of all‐cause mortality.1,2 They suggested that MAFLD could be a mediator in the association between excessive alcohol consumption and all‐cause mortality; therefore, the risk of alcohol consumption might be underestimated in our study. Although we like this suggestion of mediation, there is no evidence provided to strengthen this theory further. Moreover, we note that the mortality risk of excessive alcohol consumption did not increase (adjusted hazard rate remained 1.14) when MAFLD as a variable was left out of the analysis. Hence, we feel that it is unlikely that we underestimated the mortality risk of excessive alcohol consumption. As there was no (indirect) evidence of mediation and interaction in our study or other literature, we did not proceed with more differentiating methods to further quantify mediation and moderation simultaneously.3 Second, the authors were interested in our thought process of selecting variables included in our models. The directed acyclic graph has now been provided in this letter, illustrating the exposures, confounders, potential moderator, and outcome (Figure 1). Because of the limited number of events in the smallest group, we were restricted in the number of covariates that could be included to prevent potential overfitting. Variables were selected based on clinical relevance and previous studies in the national health and nutrition examination survey (NHANES) cohort investigating mortality and fatty liver disease, and the contribution to goodness of fit was assessed by the Akaike information criterion.4,5FIGURE 1: Directed acyclic graph of covariates with MAFLD as exposure and all‐cause mortality as outcome.Finally, multistate models were proposed to unravel further the risk of liver‐related mortality and nonliver‐related mortality for different states: "healthy," "excessive alcohol consumption," and "MAFLD." An important state lacking in this suggestion is the presence of both MAFLD and excessive alcohol consumption. However, unfortunately, liver‐related death data are not publicly available in the NHANES cohort. Yet, based on previous studies,5 only a few liver‐related deaths were recorded in this cohort. Therefore, it is unlikely that, with this data, definitive answers can be provided on liver‐related death. Hence, scientists should collaborate and unite cohorts to successfully perform multistate models and further unravel nonliver‐related and liver‐related mortality risk in individuals with excessive alcohol consumption, MAFLD, or both.
Severe Cystitis Induced by Cyclophosphamide
Authors: Bruce M. Berkson
Journal: JAMA (1973)

Hemorrhagic cystitis secondary to cyclophosphamide (Cytoxan) administration commonly responds to cessation of therapy and hydration. Occasionally, however, hemorrhage may be unresponsive to these measures. Fourteen patients with severe bladder hemorrhage described in the literature and two reported herein failed to respond and required surgical intervention. Review of the surgical procedures employed indicates that supravesical urinary diversion was promptly and consistently effective in controlling life-threatening bladder hemorrhage secondary to cyclophosphamide therapy. The pathophysiology of the disease underlies the rationale of surgical management.
Mobile Intensive Care Units
Authors: Mark A. Sherman
Journal: JAMA (1979)

Implementation of mobile intensive care units in four suburban communities permitted a retrospective evaluation of their impact on patient outcome. Data on 1,796 cases of myocardial infarction were obtained from medical records and death certificates of patients arriving at four hospitals during a 65-month period. There were statistically significant reductions in mortality rates in two communities (41.1% to 23.9% and 37.6% to 27.0%) after the service began. A reduction in one community (34.5% to 22.0%) was not statistically significant, and the fourth community showed an increase in the mortality rate (31.1% to 44.0%). Analysis of plausible rival hypotheses permitted most of these to be ruled out as causes for the observed reductions in mortality. (<i>JAMA</i>241:1899-1901, 1979)
Oral Abstract Session OAS
Journal: Allergy (2016)

Background: The complement subunit C1Q was recently identified as a marker for regulatory dendritic cells (DCreg).Furthermore, the expression of C1Q genes encoding each of its A, B and C subunits is increased in peripheral blood mononuclear cells (PBMCs) from grass pollen allergic patients exhibiting a clear clinical benefit following allergen immunotherapy (AIT).Herein, we investigated a potential direct anti-inflammatory activity of C1Q.
Reprogrammed siTNFα/neutrophil cytopharmaceuticals targeting inflamed joints for rheumatoid arthritis therapy
Authors: Yijun Chen, Kaiming Li, Mengying Jiao, Yingshuang Huang, Zihao Zhang, Lingjing Xue, Caoyun Ju, Can Zhang
Journal: Acta Pharmaceutica Sinica B (2022)

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.
Data-driven engineering framework with AI algorithm of Ginkgo Folium tablets manufacturing
Authors: Lijuan Ma, Jing Zhang, Ling Lin, Tuanjie Wang, Chaofu Ma, Xiaomeng Wang, Mingshuang Li, Yanjiang Qiao, Yongxiang Wang, Guimin Zhang, Zhisheng Wu
Journal: Acta Pharmaceutica Sinica B (2022)

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate Cpk integrated Bootstrap-t. The Cpk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.
Global prevalence of Neisseria gonorrhoeae infection in pregnant women: a systematic review and meta-analysis
Authors: Kosar Vaezzadeh, Mahdi Sepidarkish, Abolfazl Mollalo, Nayereh As'adi, Safoura Rouholamin, Mahroo Rezaeinejad, Maryam Farid Mojtahedi, Seyed Mohammad Mehdi Hosseini, Maryam Taheri, Sanaz Mahjour, Mohsen Mohammadi, Hiam Chemaitelly, Ali Rostami
Journal: Clinical Microbiology and Infection (2022)
Monocyte-derived macrophages aggravate pulmonary vasculitis via cGAS/STING/IFN-mediated nucleic acid sensing
Authors: Nina Kessler, Susanne F. Viehmann, Calvin Krollmann, Karola Mai, Katharina M. Kirschner, Hella Luksch, Prasanti Kotagiri, Alexander M.C. Böhner, Dennis Huugen, Carina C. de Oliveira Mann, Simon Otten, Stefanie A.I. Weiss, Thomas Zillinger, Kristiyana Dobrikova, Dieter E. Jenne, Rayk Behrendt, Andrea Ablasser, Eva Bartok, Gunther Hartmann, Karl-Peter Hopfner, Paul A. Lyons, Peter Boor, Angela Rösen-Wolff, Lino L. Teichmann, Peter Heeringa, Christian Kurts, Natalio Garbi
Journal: The Journal of Experimental Medicine (2022)

Autoimmune vasculitis is a group of life-threatening diseases, whose underlying pathogenic mechanisms are incompletely understood, hampering development of targeted therapies. Here, we demonstrate that patients suffering from anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) showed increased levels of cGAMP and enhanced IFN-I signature. To identify disease mechanisms and potential therapeutic targets, we developed a mouse model for pulmonary AAV that mimics severe disease in patients. Immunogenic DNA accumulated during disease onset, triggering cGAS/STING/IRF3-dependent IFN-I release that promoted endothelial damage, pulmonary hemorrhages, and lung dysfunction. Macrophage subsets played dichotomic roles in disease. While recruited monocyte-derived macrophages were major disease drivers by producing most IFN-β, resident alveolar macrophages contributed to tissue homeostasis by clearing red blood cells and limiting infiltration of IFN-β-producing macrophages. Moreover, pharmacological inhibition of STING, IFNAR-I, or its downstream JAK/STAT signaling reduced disease severity and accelerated recovery. Our study unveils the importance of STING/IFN-I axis in promoting pulmonary AAV progression and identifies cellular and molecular targets to ameliorate disease outcomes.
Probing Mutant <i>KRAS</i>, <i>STK11, KEAP1</i> in NSCLC
Journal: Cancer Discovery (2022)

Abstract According to an exploratory analysis of data from the POSEIDON trial, patients with non–small cell lung cancer and KRAS, STK11, or KEAP1 mutations fared better on the three-drug combination of tremelimumab and durvalumab plus chemotherapy compared with chemotherapy alone. However, small sample sizes precluded any definitive interpretation of the findings.
Early initiation of short‐term emollient use for the prevention of atopic dermatitis in high‐risk infants—The STOP‐AD randomised controlled trial
Authors: Carol Ní Chaoimh, Dhanis Lad, Claudio Nico, Gerwin J. Puppels, X. F. Colin C. Wong, John E. Common, Deirdre M. Murray, Alan D. Irvine, Jonathan O’Brien Hourihane
Journal: Allergy (2022)

Abstract Background Protecting the skin barrier in early infancy may prevent atopic dermatitis (AD). We investigated if daily emollient use from birth to 2 months reduced AD incidence in high‐risk infants at 12 months. Methods This was a single‐center, two‐armed, investigator‐blinded, randomized controlled clinical trial (NCT03871998). Term infants identified as high risk for AD (parental history of AD, asthma or allergic rhinitis) were recruited within 4 days of birth and randomised 1:1 to either twice‐daily emollient application for the first 8 weeks of life (intervention group), using an emollient specifically formulated for very dry, AD‐prone skin, or to standard routine skin care (control group). The primary outcome was cumulative AD incidence at 12 months. AD &lt;6 months was diagnosed based on clinical presence of AD. The UK Working Party Diagnostic Criteria were applied when diagnosing AD between 6 and 12 months. Results Three hundred twenty‐one were randomised (161 intervention and 160 control), with 61 withdrawals (41 intervention, 20 control). The cumulative incidence of AD at 12 months was 32.8% in the intervention group vs. 46.4% in the control group, p = 0.036 [Relative risk (95%CI): 0.707 (0.516, 0.965)]. One infant in the intervention group was withdrawn from the study following development of a rash that had a potential relationship with the emollient. There was no significant difference in the incidence of skin infections between the intervention and control groups during the intervention period (5.0% vs. 5.7%, p &gt; 0.05). Conclusions This study has demonstrated that early initiation of daily specialized emollient use until 2 months reduces the incidence of AD in the first year of life in high‐risk infants.